1. Field of the Invention
This invention relates to a solidified pharmaceutical composition comprising microbial cell wall skeleton which has potent adjuvant and antitumor activities.
More particularly, this invention relates to a solidified pharmaceutical composition comprising microbial cell wall skeleton, a vehicle oil, a suspending agent and a dispersing agent, which is useful as an immunotherapeutic agent for human tumors, and to a method for preparing the same.
2. Description of the Prior Art
It was reported that the cell wall skeleton (hereinafter referred to as "CWS") derived from microorganisms such as the genus Mycobacterium (e.g. Mycobacterium bovis BCG), Nocardia (e.g. Nocardia rubra) or the like has adjuvant and antitumor activities. However, since the CWS is a water-insoluble substance, it could not be administered in a form of conventional aqueous injection preparation to human body, and accordingly, for effective administration to human body for therapy, it was indispensable to apply it in a form of suspension, and the CWS was formulated as an oil-attached form and then made into oil-in-water suspension as an effective preparation for use. For example, it was reported that the CWS of Mycobacterium bovis BCG, which was treated with a mineral oil (e.g. Drakeol 6 VR) and suspended in saline-0.2% Tween 80 (trade name) was effective for the suppression of tumor growth or regression of established tumor in animals [I. Azuma et al, Gann (cancer), 65, 493-505(1974); T. Yoshimoto et al, Gann (Cancer), 67, 441-445(1976) and B. Zbar, et al J. Nath. Cancer Inst., 52, 1571-1577(1974)], and such oil-attached BCG CWS was effective for the prolongation of survival period and improvement of immunological status of tumor-bearing patients [Y. Yamamura, et al, Gann (Cancer), 67, 669-677 (1976), Y. Yamamura, et al, Gann (Cancer), 66, 355-363 (1975) and K. Yasumoto, et al, Gann (Cancer), 67, 787-795 (1976)].
As explained above, although the oil-attached CWS has many advantages in the aspects of complication and quality control as immunotherapeutic agents in comparison with living microorganisms, there were problems with its use in that suspensions of oil-attached CWS were unstable and unable to keep at the same condition more than a day so that the preparations deteriorated in quality and trended to decrease of the potency of activities thereof. Accordingly, it has been needed to prepare said suspension of oil-attached CWS every time immediately before use, i.e. administration to patients, but, since this is very complicated and inconvenient for therapy, it has been substantially impossible to use such suspension preparation for practical therapy in the required location in the hospital.